21-32694317-GA-G

Position:

• chr21-32694317-GA-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_203446.3(SYNJ1):​c.706-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,494,478 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: SYNJ1 NM_203446.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.65

Genes affected

SYNJ1 (HGNC:11503): (synaptojanin 1) This gene encodes a phosphoinositide phosphatase that regulates levels of membrane phosphatidylinositol-4,5-bisphosphate. As such, expression of this enzyme may affect synaptic transmission and membrane trafficking. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 21-32694317-GA-G is Benign according to our data. Variant chr21-32694317-GA-G is described in ClinVar as [Benign]. Clinvar id is 793252.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr21-32694317-GA-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ1	NM_203446.3	c.706-7delT		splice_region_variant, intron_variant		ENST00000674351.1	NP_982271.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNJ1	ENST00000674351.1	c.706-7delT		splice_region_variant, intron_variant			NM_203446.3	ENSP00000501530.1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000977

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000379 AC: 51 AN: 1344200 Hom.: 0 Cov.: 27 AF XY: 0.0000405 AC XY: 27 AN XY: 667072

Gnomad4 AFR exome AF: 0.000216

Gnomad4 AMR exome AF: 0.000187

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000298

Gnomad4 SAS exome AF: 0.0000708

Gnomad4 FIN exome AF: 0.0000399

Gnomad4 NFE exome AF: 0.0000285

Gnomad4 OTH exome AF: 0.0000366

GnomAD4 genome AF: 0.0000266 AC: 4 AN: 150278 Hom.: 0 Cov.: 32 AF XY: 0.0000273 AC XY: 2 AN XY: 73262

Gnomad4 AFR AF: 0.0000974

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs202044634; hg19: chr21-34066627;